Under strict embargo until 19.00 British Time Thursday 11 November 2004

GENETIC MAKE-UP MAY DETERMINE WHAT TYPE OF CJD OCCURS WHEN HUMANS AREINFECTED WITH BSE

New research published today (19.00 hours Thursday 11th November) by ateam from the Medical Research Council (MRC) Prion Unit offers anexplanation about why only people with a particular genetic make-up haveso far developed vCJD. It also provides evidence that other types ofBSE-derived prion infection with a different pattern of symptoms mightoccur in humans. The findings are published in the journal Science.

Variant CJD (vCJD) is the human disease thought to be caused by eatingfood contaminated with the infectious agent, known as a prion,responsible for the epidemic of BSE or mad cow disease in cattle. Sofar, everyone known to have developed vCJD has been of a particulargenetic type known as MM. Until now it has been a mystery why everyonethat has developed vCJD is of the MM type and one possibility is thatthey are simply the first to develop the disease when infected with BSE,and that people with the other genetic types1 (known as VV and MV)infected with BSE prions will also develop vCJD, but some years later.

In a series of experiments spanning more than ten years, the MRC teamhas been studying mice genetically modified so that they make humanprion proteins which are used to model human susceptibility to BSE.The team has now shown that mice with the human VV genetic type dobecome infected when given BSE or vCJD prions, but manifest a differentform of the disease which looks quite different to vCJD and has a novelprion strain type.

Remarkably, when these novel prions were used to infect mice of the MMgenetic type, the mice either developed a disease very like vCJD, orelse a pattern of disease that looks like so-called sporadic CJD theclassical form of CJD. This form has been known about for many years,is seen all over the world and has not hitherto been associated withBSE. However, the new strain identified in the mice, being called type5, has not been seen yet in people and we do not know what pattern ofdisease it would cause. It could look like one of the forms of classicalor sporadic CJD or perhaps be yet another different variant form.

The work from the MRC team suggests that type 4 prions, the typeassociated with vCJD, can only propagate themselves in people that makethe M form of the protein. It seems the V form of the protein justcannot adopt the particular molecular shape that characterises type 4.

The studies in mice also suggest that if these prions were to pass fromperson to person (for example by blood transfusion) then, depending onthe genetic type of the person becoming infected, at least threedifferent patterns of disease might result: type 2 (which is seen insporadic CJD); type 4 (which causes vCJD) or type 5 (which may cause anew pattern of disease).

Professor John Collinge, Director of the MRC Prion Unit, which is basedat University College London, said: These mouse studies give us vitalclues about the behaviour of prions and how they appear to modify andadapt depending on the genetic makeup of the individual they are infecting.

We always have to be cautious about making direct comparison to thehuman condition, but our work strongly suggests that we can not assumeonly those with one genetic profile are vulnerable to BSE infection.

At this stage it is not possible to say how this should alter estimatesof those likely to become ill, but our findings do suggest we should betaking steps to draw up a more sophisticated system of categorizing thedisease so that we dont mistake BSE related infection for a version ofsporadic CJD.

ENDS

For more information call the MRC press office on 020 7 637 6011

Notes to Editors

1The human prion protein comes in two common forms, known as M and V.Because everyone has two copies of this gene, there are three possiblegenetic types: MM, MV and VV.

Prions are rogue forms of one of the bodys own proteins known as theprion protein which are misshapen. There are several different rogueor misshapen forms that can infect humans, and these different types ofprions are known as strains. This is analogous to different strains ofother germs such flu virus causing influenza or strains of salmonellacausing different forms of food poisoning for example.

The strain of prion causing vCJD is known as type 4, types 1-3 cause thedifferent forms of sporadic or classical CJD. Each strain causes adifferent pattern or type of disease. It is known that prion strains canchange or mutate when they pass between different animals.

The Medical Research Council (MRC) is a national organisation funded bythe UK tax-payer. Its business is medical research aimed at improvinghuman health; everyone stands to benefit from the outputs. The researchit supports and the scientists it trains meet the needs of the healthservices, the pharmaceutical and other health-related industries and theacademic world. MRC has funded work which has led to some of the mostsignificant discoveries and achievements in medicine in the UK. Abouthalf of the MRCs expenditure of £430 million is invested in its 40Institutes, Units and Centres. The remaining half goes in the form ofgrant support and training awards to individuals and teams inuniversities and medical schools. Web site at: http://www.mrc.ac.uk.

PLUS, if the USA continues to flagrantly ignore the _documented_ scienceto date about the known TSEs in the USA (let alone the undocumented TSEsin cattle), it is my opinion, every other Country that is dealing with BSE/TSEshould boycott the USA and demand that the SSC reclassify the USA BSE GBRII risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_any longer on this issue, should also be regarded with great suspicion aswell. NOT to leave out the OIE and it's terribly flawed system of diseasesurveillance. the OIE should make a move on CWD in the USA, and make a riskassessment on this as a threat to human health. the OIE should also changethe mathematical formula for testing of disease. this (in my opinion andothers) is terribly flawed as well. to think that a sample survey of 400or so cattle in a population of 100 million, to think this will find anything,especially after seeing how many TSE tests it took Italy and other Countriesto find 1 case of BSE (1 million rapid TSE test in less than 2 years, tofind 102 BSE cases), should be proof enough to make drastic changes of thissystem. the OIE criteria for BSE Country classification and it's interpretationis very problematic. a text that is suppose to give guidelines, but is notunderstandable, cannot be considered satisfactory. the OIE told me 2 yearsago that they were concerned with CWD, but said any changes might take years.well, two years have come and gone, and no change in relations with CWDas a human health risk. if we wait for politics and science to finally makethis connection, we very well may die before any decisions

or changes are made. this is not acceptable. we must take the politics andthe industry out of any final decisions of the Scientific community. thishas been the problem from day one with this environmental man made deathsentence. some of you may think i am exaggerating, but you only have tosee it once, you only have to watch a loved one die from this one time,and you will never forget, OR forgive...yes, i am still very angry... butthe transmission studies DO NOT lie, only the politicians and the industrydo... and they are still lying to this day...TSS

EFSA ScientificReport on the Assessment of the Geographical BSE-Risk (GBR) of the UnitedStates of America (USA)

Publication date: 20 August 2004

Adopted July 2004 (Question N° EFSA-Q-2003-083)

* 167 kB Report

* 105 kB Summary

Summary of the Scientific Report

The European Food Safety Authority and its Scientific Expert WorkingGroup on the Assessment of the Geographical Bovine SpongiformEncephalopathy (BSE) Risk (GBR) were asked by the European Commission(EC) to provide an up-to-date scientific report on the GBR in the UnitedStates of America, i.e. the likelihood of the presence of one or morecattle being infected with BSE, pre-clinically as well as clinically, inUSA. This scientific report addresses the GBR of USA as assessed in 2004based on data covering the period 1980-2003.

The BSE agent was probably imported into USA and could have reacheddomestic cattle in the middle of the eighties. These cattle imported inthe mid eighties could have been rendered in the late eighties andtherefore led to an internal challenge in the early nineties. It ispossible that imported meat and bone meal (MBM) into the USA reacheddomestic cattle and leads to an internal challenge in the early nineties.

A processing risk developed in the late 80s/early 90s when cattleimports from BSE risk countries were slaughtered or died and wereprocessed (partly) into feed, together with some imports of MBM. Thisrisk continued to exist, and grew significantly in the mid 90s whendomestic cattle, infected by imported MBM, reached processing. Given thelow stability of the system, the risk increased over the years withcontinued imports of cattle and MBM from BSE risk countries.

EFSA concludes that the current GBR level of USA is III, i.e. it islikely but not confirmed that domestic cattle are (clinically orpre-clinically) infected with the BSE-agent. As long as there are nosignificant changes in rendering or feeding, the stability remainsextremely/very unstable. Thus, the probability of cattle to be(pre-clinically or clinically) infected with the BSE-agent persistentlyincreases.